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Взаимодействие герпесвируса и призрака в неврологических заболеваниях: иммуногенетическая роль ВЛА-Е.

Человеческие герпесвирусы (HHVs) состоят из девяти патогенных членов, включая герпес-синтекс-вирус 1, герпес-синтекс-вирус 2, варицелла-зостерный вирус, вирус Эпштейн-Барр, человеческий цитомегаловир, человеческий герпесвирус 6A/B, человеческий герпесвирус 7 и связанный с Капози герпесмирус. Клинические проявления инфекции ВИЧ могут варьироваться от асимптоматических случаев до широкого спектра неврологических осложнений, начиная от таких острых заболеваний, как энцефалит, и кончая хроническими расстройствами, включая болезнь Альцгеймера и множественный склероз. Устанавливая запоздалость и под

Совпадение в аннотации оригинала
Human herpesviruses (HHVs) comprise nine pathogenic members, including herpes simplex virus 1, herpes simplex virus 2, varicella-zoster viru … idence highlights the pivotal role of the human leukocyte antigen E (HLA-E) pathway-a non-classical major histocompatibility complex class I molecule with immunomodulatory functions-in regulating virus-host interactions. Since some HHVs manipulate HLA-E to evade immune recognition, individual variability in this axis may influence neurological outcomes. In this review, we summari …

Выражения и индукции MHC классов I и II в олигодендроцитах варьируются в зависимости от возраста.

Олигодендроглия, выражающая основные молекулы гистокомпьютерного комплекса (MHC), стала представлять большой интерес для многочисленных исследований склероза (MS), однако их роль в старении все еще проясняется. Используя мышей I и II классов MHC, мы сравнили выражение MHC у неонатальных, молодых взрослых (8-16 недель) и стареющих (52 недели) мышей в исходном режиме и после стереотактических родов AAV-GFAP-IFN. Мы обнаружили, что в наивном мозге и спинном мозге присутствовали MHC класса I, выражающие олигодендроглию, в то время как MHC II-выражающий олигодендроглия был виден только в спинном мо

Совпадение в аннотации оригинала
Oligodendroglia expressing major histocompatibility complex (MHC) molecules have become of central interest in multiple sclerosis (MS) research, but their role in aging is still being elucidated. Using MHC class I and II reporter mice, we compared oligodendroglial MHC expression in neonatal, young adult (8-16 weeks), and aging (52 weeks) mice at baseline and…

Aire mediates tolerance to insulin through thymic trimming of high-affinity T cell clones.

Insulin is a central autoantigen in the pathogenesis of T1D, and thymic epithelial cell expression of insulin under the control of the Autoi … umber of unique t cell receptor (TCR) clones in Aire-deficient hosts with high affinity for insulin/major histocompatibility complex (MHC) ligands. We then modeled the thymic selection of one of these clones in Aire-deficient versus wild-type hosts and found that this model clone could escape thymic negative selection in the absence of thymic Aire. Together, these results suggest …

Completing the pieces of a puzzle: in-depth probing of Toxoplasma gondii rhoptry protein 4 as a promising target for vaccination using an in-silico approach.

The present study aimed to evaluate the key characteristics of Toxoplasma gondii rhoptry protein 4 (TgROP4), including physicochemical param … Pro. The IEDB findings showed T-cell epitopes on TgROP4 protein are capable to strongly bind to the major histocompatibility complex classes. In silico immune simulation was performed using C-ImmSim server and showed three injections of TgROP4 protein at 4-week intervals is capable to elicit adequate humoral and cell-mediated immune responses.

Controversial role of γδ T cells in colorectal cancer.

Colorectal cancer (CRC) is the third most frequent type of cancer, and the second leading cause of cancer-related deaths worldwide. Current treatments for patients with CRC do not substantially improve the survival and quality of life of patients with advanced CRC, thus necessitating the development of new treatment strategies. The emergence of immunotherapy has revitalized the field, showing great potential in advanced CRC treatment. Owing to the ability of tumor cells to evade the immune system through major histocompatibility complex shedding and heterogeneous and low antigen spreading, onl…

CD276-dependent efferocytosis by tumor-associated macrophages promotes immune evasion in bladder cancer.

Interplay between innate and adaptive immune cells is important for the antitumor immune response. However, the tumor microenvironment may t … show that genetic ablation of CD276 in TAMs blocks efferocytosis and enhances the expression of the major histocompatibility complex class II (MHCII) of TAMs. This in turn increases CD4 + and cytotoxic CD8 + T cell infiltration of the tumor. Combined single cell RNA sequencing and functional experiments reveal that CD276 activates the lysosomal signaling pathway and the transcrip …

Antigen presentation plays positive roles in the regenerative response to cardiac injury in zebrafish.

In contrast to adult mammals, adult zebrafish can fully regenerate injured cardiac tissue, and this regeneration process requires an adequat … a.k.a. Cd4+ T cells, lie in close physical proximity to these antigen-presenting EdCs. We targeted Major Histocompatibility Complex (MHC) class II antigen presentation by generating cd74a; cd74b mutants, which display a defective immune response. In these mutants, Cd4+ T cells and activated EdCs fail to efficiently populate the injured tissue and EdC proliferation is significant …

Spatial proteomics reveals phenotypic and functional differences in T cell and macrophage subsets during villitis of unknown etiology.

Villitis of unknown etiology (VUE) is a prevalent inflammatory pathology of the placenta characterized by infiltration of maternal T cells a … ocation (villi vs. decidua). Additionally, villous macrophages in VUE upregulated costimulatory and major histocompatibility complex class I and II molecules compared to controls and macrophage subtypes in the decidua. Data herein provides new mechanistic insights into T cell and macrophage biology in VUE which contribute to this abnormal immune response to pregnancy.

Identification of virus epitopes and reactive T-cell receptors from memory T cells without peptide synthesis.

Identifying epitopes and their corresponding T-cell receptor (TCR) sequences is crucial in the face of rapidly mutating viruses. Peptide synthesis is often required to confirm the exact epitope sequences, which is time-consuming and expensive. In this study, we introduce a scalable workflow to identify the exact sequences of virus epitopes and reactive TCRs targeting the epitopes from memory T cells. Following the narrowing down of epitopes to specific regions via the tandem minigene (TMG) system, our workflow incorporates the utilization of peptide-major histocompatibility complex-displaying …

Current biomarkers in inclusion body myositis.

Inclusion body myositis (IBM) is an idiopathic muscle disorder primarily affecting adults above the age of 50. IBM is characterized by weakn … e immune system is also largely implicated in pathogenesis, as skeletal muscle in IBM overexpresses major histocompatibility complex I (MHC-I), and cluster of differentiation (CD) 8+ T-cells, and features endomysial inflammation. Antibodies to the cytosolic 5'-nucleotidase 1A (cN1A) protein have been associated with IBM but have low sensitivity and specificity. As many classic fe …

A clearer vision: insights into juvenile idiopathic arthritis-associated uveitis.

The aim of this narrative review is to synthesize existing evidence-based knowledge on juvenile idiopathic arthritis-associated uveitis (JIA … inuclear antibody (ANA) positivity, and the oligoarticular subtype of JIA, along with some specific major histocompatibility complex genes. Certain laboratory biomarkers, such as ANA, rheumatoid factor, interferon-λ, erythrocyte sedimentation rate, and transthyretin, have been used in JIA-U diagnosis, progress monitoring, and prognostication. Clinical features of JIA-U can range …

HLA-DRB5 Overexpression Promotes Platelet Reduction in Immune Thrombocytopenia Mice Model by Facilitating MHC-II-Mediated Antigen Presentation.

INTRODUCTION: Major histocompatibility complex II (MHC-II)-mediated antigen presentation contributes to the pathogenesis of immune thrombocytopenia (ITP). Human leukocyte antigen (HLA)-DRB5 is an MHC-II molecule and this study aims to investigate its role and mechanisms in ITP development. METHODS: Guinea pig anti-mouse platelet (PLT) serum-induced ITP mice received tail vein injection of HLA-DRB5 overexpressing adenoviral vector/immune receptor expressed on myeloid cells-1 (IREM-1) monoclonal antibody (mAb). PLT count changes in mice blood were assessed by a hematology analyzer. MHC-II/CD80/…

Dendritic cell-mediated responses to secreted Cryptosporidium effectors promote parasite-specific CD8+ T cell responses.

Cryptosporidium causes debilitating diarrheal disease in patients with primary and acquired defects in T cell function. However, it has been a challenge to understand how this infection generates T cell responses and how they mediate parasite control. Here, Cryptosporidium was engineered to express a parasite effector protein (MEDLE-2) that contains the major histocompatibility complex-I restricted SIINFEKL epitope which is recognized by T cell receptor transgenic OT-I(OVA-TCR-I) clusters of differentiation (CD)8+ T cells. These modified parasites induced expansion of endogenous SIINFEKL-speci…

Structural insights into the binding of nanobodies to the Staphylococcal enterotoxin B.

Staphylococcal Enterotoxin Type B (SEB), produced by Staphylococcus aureus bacteria, is notorious for inducing severe food poisoning and tox … Nb3, Nb8, Nb11, and Nb20 bind to SEB at the T-cell receptor (TCR) interface, while Nb6 binds at the major histocompatibility complex (MHC) interface, suggesting their potential to inhibit SEB function by disrupting interactions with TCR or MHC molecules. Molecular biological analyses confirmed the thermodynamic and kinetic parameters of Nb3, Nb5, Nb6, Nb8, Nb11, Nb15, Nb18, and N …

Interferon-γ elicits the ocular surface pathology mimicking dry eye through direct modulation of resident corneal cells.

Despite accumulating evidence indicating a key role of interferon-γ (IFN-γ)-producing immune cells in ocular infection and immunity, little is known about the direct effects of IFN-γ on resident corneal cells or on the ocular surface. Here, we report that IFN-γ impacts corneal stromal fibroblasts and epithelial cells to promote inflammation, opacification, and barrier disruption on the ocular surface, leading to dry eye. Our results demonstrated that IFN-γ dose-dependently induced cytotoxicity, pro-inflammatory cytokine/chemokine production, and expression of major histocompatibility complex c…

Gene Targets of CAR-T Cell Therapy for Glioblastoma.

Glioblastoma (GBM) is an aggressive primary brain tumor with a poor prognosis following conventional therapeutic interventions. Moreover, the blood-brain barrier (BBB) severely impedes the permeation of chemotherapy drugs, thereby reducing their efficacy. Consequently, it is essential to develop novel GBM treatment methods. A novel kind of pericyte immunotherapy known as chimeric antigen receptor T (CAR-T) cell treatment uses CAR-T cells to target and destroy tumor cells without the aid of the antigen with great specificity and in a manner that is not major histocompatibility complex (MHC)-res…

Oncolytic α-herpesvirus and myeloid-tropic cytomegalovirus cooperatively enhance systemic antitumor responses.

Oncolytic virotherapy aims to activate host antitumor immunity. In responsive tumors, intratumorally injected herpes simplex viruses (HSVs) … ntrol of both injected and distant contralateral tumors. Deletion of mCMV genes m06, which degrades major histocompatibility complex class I (MHC class I), or m144, a viral MHC class I homolog that inhibits NK activation, was shown to diminish the antitumor activity of the HSV/mCMV combination. However, an mCMV recombinant lacking the m04 gene, which escorts MHC class I to the ce …

Bioinformatics analysis identified immune infiltration, risk and drug prediction models of copper-induced death genes involved in salivary glands damage of primary Sjögren's syndrome.

This study aimed to identify copper-induced death genes in primary Sjögren's syndrome (pSS) and explore immune infiltration, risk and drug p … gulatory T cells (Treg). In immune functions, copper-induced death genes were strongly expressed in major histocompatibility complex (MHC) class I, human leukocyte antigen (HLA) and type I interferon (IFN) response. Correlation analysis showed that 5 genes including SLC31A1, PDHA1, DLD, ATP7B, and ATP7A were significantly correlated with immune infiltration. The nomogram suggeste …

Identification of Novel Loci Shared by Juvenile Idiopathic Arthritis Subtypes Through Integrative Genetic Analysis.

OBJECTIVE: Juvenile idiopathic arthritis (JIA) is the most common chronic immune-mediated joint disease among children and encompasses a het … drug targets and drug repurposing opportunities by in silico analyses. RESULTS: In addition to the major histocompatibility complex locus, we identified 15 genome-wide significant loci shared between at least 2 JIA subtypes, including 10 novel loci. Functional annotation indicated that candidate genes at these loci were expressed in diverse immune cell types. CONCLUSION: This s …

The immune-suppressive landscape in lepromatous leprosy revealed by single-cell RNA sequencing.

Lepromatous leprosy (L-LEP), caused by the massive proliferation of Mycobacterium leprae primarily in macrophages, is an ideal disease model for investigating the molecular mechanism of intracellular bacteria evading or modulating host immune response. Here, we performed single-cell RNA sequencing of both skin biopsies and peripheral blood mononuclear cells (PBMCs) of L-LEP patients and healthy controls. In L-LEP lesions, we revealed remarkable upregulation of APOE expression that showed a negative correlation with the major histocompatibility complex II gene HLA-DQB2 and MIF, which encodes a …